Registration Dossier

Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The test parameters documented do not totally comply with the specific testing guideline, but they are sufficient to accept the data. The test was conducted according to internationally accepted testing guidelines. Details about the read across approach are reported in the summary.

Data source

Reference
Reference Type:
publication
Title:
Safety Evaluation of a Alkaline cellulase
Author:
Greenough R.J., Everett D.J. and Stavnsbjerg M.
Year:
1991
Bibliographic source:
Fd Chem. Toxic. Vol. 29, No. 11, pp. 781-785, 1991

Materials and methods

Principles of method if other than guideline:
Groups of five male and five female rats were dosed orally by gavage with the test item, for five consecutive days with 0, 0.3, 1.0 or 3.0 g/kg body weight/day and killed 6 hours after the final dose. A further group was given a single i.p. dose of 100 mg methyl methanesulphonate/kg as a positive control. Slides of bone marrow cells were prepared and examined microscopically for chromosomal damage and mitotic indices were derived.
GLP compliance:
not specified
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
Five days
Frequency of treatment:
Daily
Post exposure period:
Animals were killed 6 hr after the final dose.
One hour before the rats were killed they were treated with democolcine to arrest cells in metaphase.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.3, 1.0 or 3.0 g/kg bw/day
Basis:

No. of animals per sex per dose:
Groups of five male and five female.
Positive control(s):
A further group of five male and five female rats was given a single i.p. dose of 100 mg methyl methanesulphonate/kg as a positive control and these rats were killed after 24 hr.

Examinations

Tissues and cell types examined:
Slides of bone marrow cells were prepared and examined microscopically for chromosomal damage and mitotic indices were derived.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Positive controls validity:
valid
Additional information on results:
There were no significant increases in chromosome aberrations, excluding gaps, in males or females at any dose level of the test item.
Female rats treated with the test item showed increases in aberrations including gaps at all doses but with no clear dose relationship and only statistically significant (chi squared = 5.02; P = 0.025) at 3.0 g/kg/day.
Treatment with the test substance had no effect on the mitotic capacity of bone marrow cells and it was concluded that the substance was not a chromosome mutagen for the rat in vivo.

The positive control rats showed clear chromosome damage.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test substance is not a chromosome mutagen for the rat in vivo.
Executive summary:

Groups of five male and five female Sprague-Dawley rats were dosed orally by gavage with the test item, for five consecutive days with 0, 0.3, 1.0 or 3.0 g/kg body weight/day and killed 6 hours after the final dose. A further group was given a single i.p. dose of 100 mg methyl methanesulphonate/kg as a positive control and these rats were killed after 24 hours. Slides of bone marrow cells were prepared and examined microscopically for chromosomal damage and mitotic indices were derived.

The positive control rats showed clear chromosome damage.

There were no significant increases in chromosome aberrations, excluding gaps, in males or females at any dose level. Female rats showed increases in aberrations including gaps at all doses but with no clear dose relationship and only statistically significant at 3.0g/kg/day. Treatment with the test substance had no effect on the mitotic capacity of bone marrow cells.

Conclusion

The test substance is not a chromosome mutagen for the rat in vivo.